To assess the impact of alcohol and other drug use in the trucking industry, the National Transportation Safety Board, in collaboration with The National Institute on Drug Abuse investigated fatal-to-the-driver trucking accidents in eight states over a one year period. Comprehensive drug screens were performed on blood specimens collected from 168 fatally injured drivers. One or more drugs were detected in 67% of the drivers and 33% of the drivers had detectable blood concentrations of psychoactive drugs or alcohol. The most prevalent drugs were cannabinoids and ethanol, each found in 13% of the drivers. Cocaine or benzoylecgonine was found in 8% of the cases. Seven percent of the driver's blood specimens contained amphetamine or methamphetamine and 7% contained phenylpropanolamine, ephedrine, or pseudoephedrine. A panel of toxicologists reviewed the accident investigation report and the toxicology findings for each case and determined that impairment due to marijuana use was a factor in all cases where the delta-9-tetrahydrocannabinol concentration exceeded 1.0 ng/mL and that alcohol impairment contributed to all accidents where the blood alcohol concentration was 0.04% wt/vol or greater. In 50 of 56 cases where psychoactive drugs or alcohol were found, impairment due to substance use contributed to the fatal accident.